CD33

CD33 is a transmembrane receptor expressed on cells of myeloid lineage that is involved in cell-cell interactions. It is also known as Siglec-3 (sialic acid binding Ig-like lectin 3) and gp67, and is a member of the immunoglobulin superfamily. CD33 is a therapeutic target for acute myeloid leukemia (AML).

Structure

CD33 is a 67-kDa type I transmembrane glycoprotein that belongs to the sialoadhesin family of proteins. It is composed of two immunoglobulin-like domains, a transmembrane region and a cytoplasmic tail that contains two immunoreceptor tyrosine-based inhibitory motifs (ITIMs).

Function

CD33 plays a role in cell-cell interactions during the immune response. It is involved in the negative regulation of cellular activation and proliferation. CD33 can mediate the endocytosis of ligand-bound receptors, and may also function in the intracellular trafficking of lysosomal constituents.

Clinical significance

CD33 is expressed on most leukemic blast cells in acute myeloid leukemia (AML), and is thus a target for immunotherapy. The anti-CD33 monoclonal antibody, gemtuzumab ozogamicin, was used for the treatment of AML, but was withdrawn from the market due to safety concerns. However, it was reapproved by the FDA in 2017 for the treatment of adults with newly diagnosed CD33-positive AML, and for patients aged 2 years and older with relapsed or refractory CD33-positive AML.

See also

• Acute myeloid leukemia
• Immunotherapy
• Gemtuzumab ozogamicin